Variant chr10-3144334-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014889.4(PITRM1):c.2490C>G(p.Ala830Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00812 in 1,562,510 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0084 ( 85 hom. )

Consequence

PITRM1
NM_014889.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.66

Variant links:

Genes affected

PITRM1 (HGNC:17663): (pitrilysin metallopeptidase 1) The protein encoded by this gene is an ATP-dependent metalloprotease that degrades post-cleavage mitochondrial transit peptides. The encoded protein binds zinc and can also degrade amyloid beta A4 protein, suggesting a possible role in Alzheimer's disease. [provided by RefSeq, Dec 2016]

PITRM1 links:

PITRM1-AS1 (HGNC:44675): (PITRM1 antisense RNA 1)

PITRM1-AS1 links:

ENSG00000278419 (HGNC:):

ENSG00000278419 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 10-3144334-G-C is Benign according to our data. Variant chr10-3144334-G-C is described in ClinVar as [Benign]. Clinvar id is 1666348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0084 (11847/1410348) while in subpopulation MID AF= 0.0241 (138/5722). AF 95% confidence interval is 0.0208. There are 85 homozygotes in gnomad4_exome. There are 6015 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITRM1	NM_014889.4 link	c.2490C>G	p.Ala830Ala	synonymous_variant	22/27	ENST00000224949.9	NP_055704.2	Q5JRX3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITRM1	ENST00000224949.9 link	c.2490C>G	p.Ala830Ala	synonymous_variant	22/27	1	NM_014889.4	ENSP00000224949.4		Q5JRX3-1

Frequencies

GnomAD3 genomes

AF:

0.00555

AC:

844

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.0108

Gnomad SAS

AF:

0.0127

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00772

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00777

AC:

1352

AN:

174066

Hom.:

AF XY:

0.00885

AC XY:

820

AN XY:

92604

show subpopulations

Gnomad AFR exome

AF:

0.00106

Gnomad AMR exome

AF:

0.00404

Gnomad ASJ exome

AF:

0.0194

Gnomad EAS exome

AF:

0.00969

Gnomad SAS exome

AF:

0.0140

Gnomad FIN exome

AF:

0.000969

Gnomad NFE exome

AF:

0.00767

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.00840

AC:

11847

AN:

1410348

Hom.:

Cov.:

AF XY:

0.00863

AC XY:

6015

AN XY:

696768

show subpopulations

Gnomad4 AFR exome

AF:

0.00159

Gnomad4 AMR exome

AF:

0.00379

Gnomad4 ASJ exome

AF:

0.0187

Gnomad4 EAS exome

AF:

0.0107

Gnomad4 SAS exome

AF:

0.0144

Gnomad4 FIN exome

AF:

0.00116

Gnomad4 NFE exome

AF:

0.00820

Gnomad4 OTH exome

AF:

0.00932

GnomAD4 genome

AF:

0.00553

AC:

842

AN:

152162

Hom.:

Cov.:

AF XY:

0.00512

AC XY:

381

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00130

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.0106

Gnomad4 SAS

AF:

0.0127

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00772

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00891

Hom.:

Bravo

AF:

0.00535

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	PITRM1: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 12, 2024	- -

PITRM1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.091

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over